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Incidence of, risk factors for, histological features of and protein expression patterns in injection site sarcomas in cats - VM0131

Recent studies have suggested a causal association between injections and the development of fibrosarcomas at the injection sites in cats. There is a critical need for a rigorous study of factors associated with the development of feline injection site fibrosarcomas (FISS) in the UK, as detailed by the Veterinary Products Committee (VPC) Working Group on Feline and Canine Vaccination. The primary hypothesis of this study is that vaccination or drug administration is associated with the occurrence of these tumours at sites commonly used for injection. The true incidence of (FISS) is unknown, with estimates varying from 1 case in 20,000 cats to as high as 1 case in 1,000 cats per year. A second aim of this study is to estimate the incidence of FISS in cats in the UK.

FISS represent a group of neoplasms that have been recognised for some years as having a distinct anatomical location (usually on the dorsal midline of the thorax/neck) and have an aggressive clinical growth habit, with wide local infiltration into the surrounding tissues of the neck and thorax. These tumours have a heterogenous histological appearance and this often leads to a number of different diagnoses being given to these tumours, such as fibrosarcomas, leiomyosarcomas, malignant fibrous or histiocytoma. Since this group of tumours has been poorly defined in the veterinary literature, a third aim of this study, that is essential to the case-control study, is to create an expert consensus of opinion on the histological characteristics of this tumour type that can be used as consistent diagnostic criteria. The histopathological component of the study will allow accurate identification of cases of FISS in the present case-control and future studies.

FISS have been associated with upregulated expression of a number of growth factors including platelet-derived growth factor, epidermal growth factor, transforming growth factor b and their receptors while non-injection site sarcomas show weak expression of these growth factors. A final aim of this study is to classify these tumours using a proteomics-based approach to characterise differences in protein expression between injection site sarcomas and sarcomas arising at non-injection sites.

This study will address the concerns of practitioners, industry representatives, government agencies, associations with an interest in the health of pets and pet owners by providing high quality data on the frequency of occurrence of injection site sarcomas in cats. The findings of this study will also have an impact on cat welfare as estimates of the incidence of and identification of risk factors for FISS may help to allay owner fears about the magnitude of the risk of vaccination. The proteomics study may identify molecular markers of FISS and should offer new insights into the pathogenesis and possible novel treatments for the disease. The findings of this study will generate refined hypotheses that can be tested in future targeted studies investigating the pathogenesis of FISS.
1. To form a consensus of expert opinion on the histological features of FISS and determine the histological criteria required for case definition in the epidemiological component of the study. Consistent diagnostic criteria are required in order to have confidence in the case definition subsequently used for incidence estimates and identification and quantification of risk factors.

2. To identify the protein expression profile of injection site sarcomas in comparison to sarcomas arising at non-injection sites.

3. To estimate the incidence of injection site sarcomas in the UK using a source population of cats who are registered with a sample of veterinary practices during the study period as the denominator.

To identify factors related to the occurrence of injection site sarcomas. Specifically:

4. To determine the lifetime risk for individual cats and whether the administration of multiple injections at the same anatomical location modifies this risk.

5. To determine whether the use of adjuvanted inactivated vaccines is associated with a greater risk compared to non-adjuvanted vaccines or other injections.

6. To determine whether there is heterogeneity of risk within classes of vaccine antigen (e.g. FVRCP trivalent vaccine, FVRCP + FeLV 4-way vaccine, FeLV monovalent vaccine, etc.) or drug (e.g. long-acting penicillin, corticosteroids, etc.).

7. To determine whether other factors such as the placement of microchips, use of topical insecticides or the occurrence of abscesses/bite wounds are associated with, or modify, the occurrence of these tumours.
Project Documents
• FRP - Final Report : VM0131 sid5   (892k)
Time-Scale and Cost
From: 2005

To: 2009

Cost: £281,037
Contractor / Funded Organisations
Animal Health Trust
Animal Health              
Plants and Animals              
Veterinary Medicines              
Fields of Study
Animal Health
Veterinary Medicine